BCG-CpG-DNA一般毒性的初步评价  

Preliminary Evaluation on General Toxicity of BCG-CpG-DNA

作　　者：赵爱华[1] 乔来艳[1] 贾淑珍[1] 寇丽杰[1] 王雯[1] 李凤祥[1] 王国治[1] 

机构地区：[1]中国药品生物制品检定所菌苗室,北京100050

出　　处：《中国生物制品学杂志》2010年第8期797-802,共6页Chinese Journal of Biologicals

基　　金：十一五863项目(2006AA02A240)

摘　　要：目的观察BCG-CpG-DNA对小鼠急性毒性和28d长期毒性作用,评价其一般毒性。方法小鼠分别经背部皮下给予BCG-CpG-DNA100、250和500μg1次(急性毒性试验)和7次(28d长期毒性试验),对照组注射生理盐水。单次给药后观察小鼠的生长情况和体重变化,14d后观察脏器是否发生病变;重复给药期间及末次给药后3周恢复期内,每周观察小鼠外观体征、局部刺激性和体重变化;末次给药后3d及3周检测血液学、血液生化学指标及主要脏器系数和抗双链DNA抗体水平。结果 BCG-CpG-DNA急性毒性试验中,各组小鼠均健康存活,体重增加,无毒性反应。BCG-CpG-DNA28d长期毒性试验中,动物体重、行为活动无异常,给药部位无局部刺激性表现;BCG-CpG-DNA重复给药可提高小鼠免疫细胞的数量;末次给药后3d,各试验组脾脏系数均高于对照组,且差异有统计学意义(P<0.05),经过3周恢复期回复正常;各试验组血清中抗双链DNA水平与对照组比较,差异无统计学意义,均低于25U/ml的临界值。结论 BCG-CpG-DNA主要影响小鼠的免疫细胞和免疫器官,未见其他明显的急性毒性和长期毒性作用,表明BCG-CpG-DNA具有较好的安全性。Objective To observe the acute and chronic toxicities of BCG-CpG-DNA in mice and evaluate the general toxicity. Methods Eighty KM mice were divided into one control and three test groups, 20 for each. The mice in control group were s. c. injected once with physiological saline, while those in three test groups once with 100, 250 and 500 μg of BCG-CpG-DNA for acute toxicity test. However, another 80 mice were grouped by the same method and injected for 7 times on days 0, 3, 7, 10, 14, 21 and 28 respectively for chronic toxicity test. The growth, bodyweight and pathological change of mice in acute toxicity test were observed. The physical signs, local irritations and body weights of mice were observed once a week until 3 weeks after the last injection. The haematological and blood biochemical indexes, main organ coefficients as well as anti-dsDNA antibody levels of mice were determined 3 d and 3 weeks after the last injection. Results In acute toxicity test, all the mice survived with bodyweights gained and showed no toxic reaction. In chronic toxicity test, no abnormalities in the bodyweights or behaviors or local irritation of mice were observed. Repeat administration with BCG-CpG-DNA increased the immune cell counts of mice. The spleen coefficients of mice in various test groups 3 d after the last injection were significantly higher than those in control groups （P 0. 05）, which recovered to the normal level 3 weeks later. The anti-dsDNA antibody levels in sera of mice in various test groups showed no significant difference with those in control group, both of which were less than a cutoff value of 25 U / ml. Conclusion BCG-CpG-DNA mainly affected the immune cells and immune organs of mice, while showed no significantly acute or chronic toxicities, indicating good safety.

关 键 词：BCG-CPG-DNA 毒性试验 安全性评价 

分 类 号：R392-33[医药卫生—免疫学]